Synthesis of indene and naphthalene derivatives by a palladium-catalyzed domino carbopalladation/cyclization/coupling process

Article abstract of DOI:10.1002/ejoc.200701043

Highly substituted indene and naphthalene derivatives have been readily prepared in good-to-high yields by a palladium-catalyzed domino reaction. This domino reaction involves a Heck carbopalladation/cyclization/coupling process. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200701043

FULL PAPER
DOI: 10.1002/ejoc.200701043
Synthesis of Indene and Naphthalene Derivatives by a Palladium-Catalyzed
Domino Carbopalladation/Cyclization/Coupling Process
Li-Na Guo,[a] Xin-Hua Duan,[a] Jie Hu,[a] Hai-Peng Bi,[a] Xue-Yuan Liu,[a] and
Yong-Min Liang*[a,b]
Keywords: Domino reactions / Carbopalladation / Cyclization / C-C coupling
Highly substituted indene and naphthalene derivatives have
been readily prepared in good-to-high yields by a palladium-
catalyzed domino reaction. This domino reaction involves a
Heck carbopalladation/cyclization/coupling process.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
of highly substituted indene and naphthalene derivatives by
the palladium-catalyzed Heck/Suzuki–Miyaura, Heck/
Sonogashira and Heck/Heck domino reactions (Scheme 2).
Introduction
Transition-metal-catalyzed domino reactions are versa-
tile and powerful tools of contemporary organic synthe-
sis.[1,2] In particular, palladium-catalyzed domino cycliza-
tion reactions based on sequences of insertions of organ-
opalladium species into multiple bonds have attracted great
interest because these processes allow a considerable in-
crease in the molecular complexity in a single operation and
usually proceed with excellent chemo-, regio- and stereose-
lectivity under mild conditions.[3–5] They also greatly en-
hance the efficiency of the synthesis and minimize the
amount of reagents required.
Carbocycles and heterocycles are extremely important
and basic skeletons of many biologically active natural
products with specific structures. The palladium-catalyzed
annulation of alkynes is particularly effective for the synthe-
sis of a wide variety of carbocycles and heterocycles.[6] On
the other hand, domino reactions initiated by intramolecu-
lar Heck reactions have been developed and advanced to
prepare complex molecules in a single operation.[3–5] The
key step in these reactions is the syn addition of arylpalla-
dium halide to the triple bond which affords an intermedi-
ate that can participate in a wide variety of useful synthetic
processes. Recently, we successfully employed the annu-
lation of alkynes in the synthesis of various highly substi-
tuted indenes (Scheme 1).[7] Pursuing our interest in con-
structing carbocycles, we herein wish to report the synthesis
Scheme 1.
Results and Discussion
To find the optimum reaction conditions, diethyl 2-(2-
iodophenyl)-2-(3-phenylprop-2-ynyl)malonate (1a) was
used as a model compound, and a series of experiments was
performed with phenylboronic acid (2a). After a brief sur-
vey of reaction conditions, it was found that Pd(PPh3)4 gave
the best yield. Among bases such as K2CO3, Et3N, KOAc,
Cs2CO3 and KOtBu, K2CO3 gave the best results. DMF
was an excellent solvent.
Subsequently, the reaction with various substrates was
examined. The results of the palladium-catalyzed domino
cyclization reactions of 1 and boronic acids 2 are shown in
Table 1. The reaction of 1a (0.2 mmol) with 1.2 equiv. of
phenylboronic acid (2a) in the presence of 5 mol-%
Pd(PPh3)4 in DMF under argon at 100 °C for 2 h gave
[a] State Key Laboratory of Applied Organic Chemistry, Lanzhou
University,
Lanzhou 730000, P. R. China
Fax: +86-931-8912582
E-mail: liangym@lzu.edu.cn
[b] State Key Laboratory of Solid Lubrication, Lanzhou Institute
of Chemical Physics, Chinese Academy of Science,
Lanzhou 730000, P. R. China
diethyl
2,3-dihydro-3-(diphenylmethylene)indene-1,1-di-
carboxylate (3a) in 85% isolated yield (Table 1, entry 1).
Phenylboronic acids bearing an electron-donating or
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Synthesis of Indene and Naphthalene Derivatives
Scheme 2.
-withdrawing group in the para, ortho or meta positions tions. Similarly, the corresponding (Z)-naphthalene deriva-
usually gave good yields of the corresponding 3-substi- tives were obtained in good-to-high yields (entries 15–18).
tuted (Z)-2,3-dihydroindenes with high stereoselectivity
Meanwhile, we examined the reaction of the easily pre-
(entries 2–8). Disubstituted phenylboronic acid 2i also pared double aryl halide 1e under the same conditions by
worked well to give the indene product (Z)-3i as a single using 0.2 mmol of 1e and 2.4 equiv. of 2a. To our delight,
stereoisomer (entry 9). However, no trace of the target the reaction proceeded well at both the triple bonds and
product was isolated from the reaction of 1a with 2j (en- afforded the expected product 3m in 63% isolated yield
try 10). The reaction of substrates 1 bearing an electron- (Scheme 3). Remarkably, four carbon–carbon bonds were
donating or -withdrawing group on the aromatic ring such formed in a single step. This result clearly indicates the util-
as 1b and 1c also stereoselectively gave the desired cyclized ity of our tandem cyclization as an efficient method for the
products (E)-3k and (E)-3l, respectively, in high yields (en- synthesis of complex carbocycles.
tries 11 and 12). However, when R1 = H, a mixture of un-
To further explore the scope and versatility of this tan-
identified products was obtained (entry 13). The structure dem cyclization reaction, we next investigated the reaction
and absolute stereochemistry of (Z)-3d was unambiguously of the substrate 1a and 4 with a variety of terminal alkynes
confirmed by its X-ray crystallographic data.[8] Encouraged 6. As shown in Table 2, the Heck/Sonogashira domino reac-
by these results, we examined the reaction of substrate 4 tion proceeded well with both aliphatic and aromatic al-
with some arylboronic acids 2 under these optimized condi- kynes and afforded the corresponding products in good-to-
Table 1. Palladium-catalyzed Heck/Suzuki–Miyaura domino reaction of 1 or 4 with various boronic acids 2.[a]
Entry
R1
R2
Time [h]
3 or 5
% Yield[b]
1
2
3
4
5
6
7
8
Ph (1a)
Ph (2a)
2
3
2
5
2
2
5
5
5
5
3
2
5
5
5
5
5
5
3a
3b
85
81
83
80
95
88
87
96
56
0
87
91
–
93
92
85
89
92
1a
p-MeO-Ph (2b)
1a
p-CH3-Ph (2c)
3c
1a
p-CH3CO-Ph (2d)
3d
1a
o-MeO-Ph (2e)
3e
1a
o-CH3-Ph (2f)
3f
1a
m-CH3-Ph (2g)
3g
1a
m-NO2-Ph (2h)
3h
9
1a
2,6-dimethoxy (2i)
3i
3j
10
11
12
13
14
15
16
17
18
1a
Bu (2j)
2a
p-CH3-Ph (1b)
3k
3l
p-CH3CO-Ph (1c)
2a
H (1d)
Ph (4)
4
4
4
4
2a
mixture
5a
2a
2c
5c
2d
5d
2f
5f
2g
5g
[a] Reaction conditions: 1 or 4 (1.0 equiv.), boronic acid 2 (1.2 equiv.), K2CO3 (2.0 equiv.) and Pd(PPh3)4 (5 mol-%) in DMF at 100 °C.
[b] Isolated yield.
Eur. J. Org. Chem. 2008, 1418–1425
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L.-N. Guo, X.-H. Duan, J. Hu, H.-P. Bi, X.-Y. Liu, Y.-M. Liang
FULL PAPER
was obtained.[10,11] The E configuration of the tetrasubsti-
tuted double bond in the major diastereomer was deduced
from the NOESY spectrum by the interaction between the
proton of the double bond and the proton of the methylene
in the 2-position of the indene moiety.
Conclusions
In summary, we have developed an efficient method for
the preparation of structurally versatile indene and naph-
thalene derivatives in good-to-high yields by palladium-cat-
alyzed Heck/Suzuki–Miyaura, Heck/Sonogashira and
Heck/Heck domino reactions. This transformation leads to
the formation of two C–C bonds in a one-pot process and
high selectivity is observed for the sequential process.
Scheme 3.
high yields. The stereoselectivities were very good and only
the Z stereoisomer was formed during this reaction.[5b,9]
We then applied these methods to the synthesis of com-
pound 9 by a Heck/Heck domino reaction (Scheme 4). On
the basis of the above results, the regioselective syn insertion
of arylpalladium species into the triple bond of the diethyl
malonate alkyne was expected. However, after some trials,
a separable mixture of two stereoisomers (E,E/Z,E = 85:15)
Experimental Section
General Remarks: All reactions were performed under argon. Un-
less otherwise stated, all boronic acids and terminal alkynes were
purchased from commercial suppliers and used without further pu-
rification. Column chromatography was carried out on silica gel.
Melting points were determined with a microscopic apparatus and
are uncorrected. 1H NMR spectra were recorded in CDCl3 with
spectrometers operating at 300 or 400 MHz and 13C NMR spectra
were recorded in CDCl3 with spectrometers operating at 75 or
100 MHz with TMS as the internal standard. IR spectra were re-
corded on a FTIR spectrometer and only the major peaks are re-
ported. All products were characterized by element analysis.
General Procedure for the Preparation of Substrates 1a–1c, 1e and
4: K2CO3 (4.0 mmol) was added to a solution of diethyl (2-iodo-
phenyl)malonate (0.72 g, 2.0 mmol) and (3-bromoprop-1-ynyl)ben-
zene (2.4 mmol) in DMF (5.0 mL). The mixture was stirred for 2 h
at room temperature. Then, the reaction mixture was diluted with
EtOAc. The EtOAc solution was washed with water and saturated
brine. The organic layers were dried with Na2SO4 and concen-
trated. The residue was purified by column chromatography on sil-
ica gel to afford the corresponding substrates.
Scheme 4.
Table 2. Palladium-catalyzed Heck/Sonogashira domino reaction of 1a or 4 with various alkynes 6.[a]
Entry
1a or 4
R3
Time [h]
7 or 8
% Yield[b]
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
4
Ph (6a)
5
5
6
6
12
5
7a
7b
7c
7d
7e
8a
8b
8c
85
89
87
p-MeO-Ph (6b)
1-cyclohexenyl (6c)
TMS (6d)
n-pentyl (6e)
6a
6b
6c
91
42[c]
82
4
5
6
73
60
4
[a] Reaction conditions: 1a or 4 (1.0 equiv.), alkyne 6 (1.5 equiv.), Et3N (2.0 equiv.), CuI (10 mol-%) and Pd(PPh3)2Cl2 (5 mol-%) in DMF
at 100 °C. [b] Isolated yield. [c] The reaction was run at 60 °C.
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Eur. J. Org. Chem. 2008, 1418–1425

Synthesis of Indene and Naphthalene Derivatives
Diethyl 2-(2-Iodophenyl)-2-(3-phenylprop-2-ynyl)malonate (1a): under argon at 100 °C. When the reaction was considered complete,
Compound 1a was prepared following the above procedure, em-
ploying diethyl (2-iodophenyl)malonate (0.72 g, 2.0 mmol) and (3-
bromoprop-1-ynyl)benzene (0.47 g, 2.4 mmol) to afford 1a (0.83 g,
as determined by TLC analysis, the reaction mixture was cooled to
room temperature, quenched with a saturated aqueous solution of
ammonium chloride and extracted with EtOAc. The combined or-
ganic extracts were washed with water and saturated brine. The
1
87%) as an oil. H NMR (300 MHz, CDCl3): δ = 7.96–7.93 (dd, J
= 1.2, 8.1 Hz, 1 H), 7.37–7.24 (m, 2 H), 7.20–7.10 (m, 5 H), 7.00– organic layers were dried with Na2SO4 and filtered. The solvent
6.95 (m, 1 H), 4.41–4.21 (m, 4 H), 3.64 (s, 2 H), 1.31–1.26 (m, 6 was evaporated under reduced pressure. The residue was purified
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.7, 141.8, 139.5,
by chromatography on silica gel to afford the corresponding substi-
131.3, 130.8, 129.0, 127.9, 127.5, 123.5, 97.6, 85.8, 83.1, 66.5, 62.4,
tuted indene (3) or naphthalene (5) derivatives.
26.4, 13.8 ppm. IR (neat): ν = 3450, 2982, 1744, 1466, 1257, 1202,
˜
Diethyl 3-(Diphenylmethylene)-2,3-dihydroindene-1,1-dicarboxylate
(3a): The reaction mixture was purified by chromatography with
20:1 hexanes/EtOAc to afford 72.4 mg (85%) of the title compound
1013 cm–1.
Diethyl 2-(2-Iodophenyl)-2-[3-(p-tolyl)prop-2-ynyl]malonate (1b):
Compound 1b was prepared following the above procedure, em-
ploying diethyl (2-iodophenyl)malonate (0.72 g, 2.0 mmol) and 1-
(3-bromoprop-1-ynyl)-4-methylbenzene (0.50 g, 2.4 mmol) to af-
1
as a solid; m.p. 94–96 °C. H NMR (300 MHz, CDCl3): δ = 7.61–
7.58 (d, J = 8.1 Hz, 1 H), 7.33–7.13 (m, 11 H), 6.97–6.92 (m, 1 H),
6.47–6.44 (d, J = 7.5 Hz, 1 H), 4.23–4.16 (m, 4 H), 3.52 (s, 2 H),
1.28–1.22 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.2,
142.9, 142.1, 141.1, 136.7, 135.6, 129.6, 129.0, 128.7, 128.1, 127.9,
127.7, 127.3, 126.9, 126.5, 124.9, 63.1, 61.7, 42.4, 14.0 ppm. IR
1
ford 1b (0.86 g, 88%) as an oil. H NMR (300 MHz, CDCl3): δ =
7.96–7.93 (m, 1 H), 7.38–7.26 (m, 2 H), 7.04–6.96 (m, 5 H), 4.42–
4.21 (m, 4 H), 3.62 (s, 2 H), 2.28 (s, 3 H), 1.32–1.27 (t, J = 7.2 Hz,
6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.8, 141.8, 139.6,
137.5, 131.2, 130.8, 129.0, 128.7, 127.6, 120.4, 97.7, 84.9, 83.2, 66.6,
(KBr): ν = 3467, 2982, 1733, 1444, 1259, 1239, 1050 cm–1.
˜
C28H26O4 (426.18): calcd. C 78.85, H 6.14; found C 78.72, H 6.04.
62.5, 26.4, 21.4, 13.8 ppm. IR (neat): ν = 3442, 2982, 1744, 1466,
˜
Diethyl (Z)-3-[(4-Methoxyphenyl)(phenyl)methylene]-2,3-dihydroin-
dene-1,1-dicarboxylate (3b): The reaction mixture was purified by
1256, 1201, 1014 cm–1.
Diethyl 2-[3-(4-Acetylphenyl)prop-2-ynyl]-2-(2-iodophenyl)malonate chromatography with 20:1 hexanes/EtOAc to afford 73.9 mg (81%)
(1c): Compound 1c was prepared following the above procedure,
employing diethyl (2-iodophenyl)malonate (0.72 g, 2.0 mmol) and
4-(3-bromoprop-1-ynyl)phenylethanone (0.57 g, 2.4 mmol) to af-
ford 1c (0.95 g, 92%) as an oil. H NMR (300 MHz, CDCl3): δ =
7.98–7.95 (m, 1 H), 7.80–7.77 (d, J = 8.7 Hz, 2 H), 7.39–7.34 (m,
1 H), 7.27–7.21 (m, 1 H), 7.19–7.16 (d, J = 8.1 Hz, 2 H), 7.04–6.98
of the title compound as a solid; m.p. 133–135 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.60–7.58 (dd, J = 0.8, 7.6 Hz, 1 H), 7.34–
7.30 (m, 2 H), 7.27–7.23 (m, 3 H), 7.19–7.13 (m, 3 H), 7.01–6.97
(m, 1 H), 6.88–6.86 (m, 2 H), 6.58–6.56 (m, 1 H), 4.24–4.17 (m, 4
H), 3.82 (s, 3 H), 3.50 (s, 2 H), 1.28–1.23 (m, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.2, 158.9, 143.3, 142.0, 141.4, 136.4,
1
(m, 1 H), 4.42–4.25 (m, 4 H), 3.68 (s, 2 H), 2.55 (s, 3 H), 1.33–1.24 135.4, 134.4, 130.9, 129.1, 128.1, 127.9, 127.6, 126.9, 126.4, 124.9,
(m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 197.3, 168.7, 114.1, 63.2, 61.7, 55.2, 42.4, 14.0 ppm. IR (KBr): ν = 3468, 2982,
˜
141.9, 139.3, 135.6, 131.4, 130.7, 129.1, 128.5, 127.9, 127.6, 97.4,
1733, 1603, 1509, 1463, 1244, 1031 cm–1. C29H28O5 (456.19): calcd.
C 76.30, H 6.18; found C 76.42, H 6.07.
89.9, 82.5, 66.5, 62.6, 26.5, 26.3, 13.8 ppm. IR (neat): ν = 3448,
˜
3349, 2982, 1743, 1683, 1601, 1466, 1361, 1262, 1202, 1014 cm–1.
Diethyl (Z)-3-[Phenyl(p-tolyl)methylene]-2,3-dihydroindene-1,1-di-
carboxylate (3c): The reaction mixture was purified by chromatog-
raphy with 20:1 hexanes/EtOAc to afford 73.0 mg (83%) of the
Compound 1e: Compound 1e was prepared following the above
procedure, employing diethyl (2-iodophenyl)malonate (0.87 g,
2.4 mmol) and 1,4-bis(3-bromoprop-1-ynyl)benzene (0.31 g,
1.0 mmol) to afford 1e (0.62 g, 71%) as an oil. 1H NMR (400 MHz,
1
title compound as a solid; m.p. 148–150 °C. H NMR (400 MHz,
CDCl3): δ = 7.60–7.58 (d, J = 8.0 Hz, 1 H), 7.33–7.10 (m, 10 H),
CDCl3): δ = 7.95–7.93 (dd, J = 1.2, 7.6 Hz, 1 H), 7.36–7.29 (m, 5 7.00–6.96 (m, 1 H), 6.55–6.53 (d, J = 8.0 Hz, 1 H), 4.25–4.18 (m,
H), 7.24–7.22 (dd, J = 1.6, 8.0 Hz, 1 H), 7.00–6.95 (m, 5 H), 4.39–
4.23 (m, 8 H), 3.63 (s, 4 H), 1.32–1.27 (t, J = 7.2 Hz, 12 H) ppm.
4 H), 3.51 (s, 2 H), 2.37 (s, 3 H), 1.27–1.22 (m, 6 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.3, 143.2, 142.1, 141.3, 139.1,
13C NMR (100 MHz, CDCl3): δ = 168.5, 141.8, 139.3, 132.7, 131.1, 136.9, 136.8, 135.4, 129.5, 129.0, 128.1, 127.9, 127.6, 126.8, 126.5,
130.6, 129.0, 127.5, 122.3, 121.5, 97.4, 87.1, 82.0, 66.4, 62.4, 26.2,
125.0, 63.1, 61.7, 42.3, 21.3, 14.0 ppm. IR (KBr): ν = 3472, 2983,
˜
13.7 ppm. IR (neat): ν = 3449, 2981, 1744, 1484, 1467, 1257, 1202,
1734, 1464, 1260, 1231, 1025 cm–1. C29H28O4 (440.20): calcd. C
79.07, H 6.41; found C 79.12, H 6.37.
˜
1012 cm–1.
Diethyl 2-(2-Iodobenzyl)-2-(3-phenylprop-2-ynyl)malonate (4): Com-
pound 4 was prepared following the above procedure, employing
diethyl (2-iodobenzyl)malonate (0.75 g, 2.0 mmol) and (3-bro-
Diethyl
(Z)-3-[(4-Acetylphenyl)(phenyl)methylene]-2,3-dihydroin-
dene-1,1-dicarboxylate (3d): The reaction mixture was purified by
chromatography with 20:1 hexanes/EtOAc to afford 74.9 mg (80%)
of the title compound as a solid; m.p. 144–146 °C. 1H NMR
moprop-1-ynyl)benzene (0.47 g, 2.4 mmol) to afford 4 (0.86 g,
1
88%) as an oil. H NMR (400 MHz, CDCl3): δ = 7.84–7.81 (m, 1 (400 MHz, CDCl3): δ = 7.95–7.93 (dd, J = 2.0, 8.4 Hz, 2 H), 7.63–
H), 7.44–7.40 (m, 3 H), 7.29–7.23 (m, 4 H), 6.91–6.86 (m, 1 H),
4.30–4.14 (m, 4 H), 3.70 (s, 2 H), 3.03 (s, 2 H), 1.25–1.20 (m, 6
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.5, 139.9, 139.2,
131.5, 130.6, 128.6, 128.1, 127.9, 123.0, 102.1, 84.9, 84.2, 61.6, 58.0,
7.61 (dd, J = 0.8, 8.0 Hz, 1 H), 7.37–7.32 (m, 4 H), 7.28–7.18 (m,
4 H), 7.00–6.96 (m, 1 H), 6.51–6.49 (d, J = 7.6 Hz, 1 H), 4.25–4.19
(m, 4 H), 3.52 (s, 2 H), 2.62 (s, 3 H), 1.28–1.24 (t, J = 7.6 Hz, 6
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 197.7, 170.0, 147.2,
41.2, 24.1, 13.8 ppm. IR (neat): ν = 3466, 2981, 1732, 1468, 1439, 142.4, 142.3, 140.6, 136.8, 136.0, 135.5, 130.1, 129.0, 128.8, 128.3,
˜
1276, 1202, 1064 cm–1.
128.2, 128.1, 127.3, 126.7, 124.8, 63.1, 61.8, 42.4, 26.5, 14.0 ppm.
IR (KBr): ν = 3466, 3349, 2982, 1732, 1683, 1600, 1362, 1262, 1050,
˜
General Procedure for the Preparation of 3 and 5: A mixture of
diethyl (2-iodophenyl)-2-(3-arylprop-2-ynyl)malonate or diethyl (2-
iodobenzyl)-2-(3-phenylprop-2-ynyl)malonate (1 or 4; 0.20 mmol),
1022 cm–1. C30H28O5 (468.19): calcd. C 76.90, H 6.02; found C
76.72, H 6.17.
boronic acids
Pd(PPh3)4 (11.5 mg, 5 mol-%) and DMF (2.0 mL) was placed in a dene-1,1-dicarboxylate (3e): The reaction mixture was purified by
25 mL flask under argon. The resulting mixture was then heated chromatography with 20:1 hexanes/EtOAc to afford 86.6 mg (95%)
2 (0.24 mmol), K2CO3 (55.2 mg, 0.40 mmol), Diethyl (Z)-3-[(2-Methoxyphenyl)(phenyl)methylene]-2,3-dihydroin-
Eur. J. Org. Chem. 2008, 1418–1425
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L.-N. Guo, X.-H. Duan, J. Hu, H.-P. Bi, X.-Y. Liu, Y.-M. Liang
FULL PAPER
of the title compound as an oil. H NMR (400 MHz, CDCl3): δ =
7.59–7.57 (d, J = 7.6 Hz, 1 H), 7.35–7.28 (m, 5 H), 7.22–7.14 (m,
3 H), 6.98–6.90 (m, 3 H), 6.40–6.38 (d, J = 7.6 Hz, 1 H), 4.27–4.14
(m, 4 H), 3.62–3.47 (q, J = 16.4, 45.2 Hz, 2 H), 3.57 (s, 3 H), 1.31–
1
Diethyl (E)-3-[Phenyl(p-tolyl)methylene]-2,3-dihydroindene-1,1-di-
carboxylate (3k): The reaction mixture was purified by chromatog-
raphy with 20:1 hexanes/EtOAc to afford 76.6 mg (87%) of the title
1
compound as an oil. H NMR (300 MHz, CDCl3): δ = 7.60–7.58
1.20 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.3, 157.2, (d, J = 7.8 Hz, 1 H), 7.34–7.27 (m, 3 H), 7.24–7.11 (m, 7 H), 6.96–
142.6, 141.8, 141.4, 136.2, 133.2, 130.9, 128.9, 128.6, 128.1, 127.9,
127.5, 126.6, 126.4, 124.4, 121.1, 111.8, 63.0, 61.7, 55.6, 41.4,
6.91 (m, 1 H), 6.45–6.42 (d, J = 8.1 Hz, 1 H), 4.24–4.15 (m, 4 H),
3.54 (s, 2 H), 2.33 (s, 3 H), 1.27–1.22 (t, J = 7.2 Hz, 6 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 170.2, 142.2, 141.9, 141.3, 140.0,
136.7, 136.6, 135.1, 129.7, 128.9, 128.8, 128.7, 127.9, 127.5, 127.2,
14.0 ppm. IR (neat): ν = 3466, 2982, 1733, 1596, 1463, 1367, 1241,
˜
1049, 1026 cm–1. C29H28O5 (456.19): calcd. C 76.30, H 6.18; found
C 76.12, H 6.27.
126.4, 124.9, 63.1, 61.7, 42.3, 21.2, 14.0 ppm. IR (neat): ν = 3468,
˜
2982, 1733, 1464, 1258, 1231, 1050 cm–1. C29H28O4 (440.20): calcd.
C 79.07, H 6.41; found C 78.93, H 6.27.
Diethyl (Z)-3-[Phenyl(o-tolyl)methylene]-2,3-dihydroindene-1,1-di-
carboxylate (3f): The reaction mixture was purified by chromatog-
raphy with 20:1 hexanes/EtOAc to afford 77.4 mg (88%) of the
Diethyl
(E)-3-[(4-Acetylphenyl)(phenyl)methylene]-2,3-dihydroin-
1
dene-1,1-dicarboxylate (3l): The reaction mixture was purified by
chromatography with 20:1 hexanes/EtOAc to afford 85.2 mg (91%)
of the title compound as a solid; m.p. 77–79 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.94–7.92 (d, J = 8.4 Hz, 2 H), 7.63–7.61
(d, J = 7.8 Hz, 1 H), 7.39–7.34 (m, 5 H), 7.25–7.18 (m, 3 H), 7.00–
6.95 (m, 1 H), 6.48–6.45 (d, J = 8.1 Hz, 1 H), 4.25–4.18 (q, J =
7.2 Hz, 4 H), 3.51 (s, 2 H), 2.59 (s, 3 H), 1.28–1.23 (t, J = 7.2 Hz,
6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 197.6, 170.0, 147.7,
142.2, 141.3, 140.7, 137.2, 135.5, 135.4, 129.7, 129.2, 128.9, 128.3,
128.2, 128.0, 127.6, 126.5, 125.1, 63.0, 61.8, 42.2, 26.6, 14.0 ppm.
title compound as a solid; m.p. 111–113 °C. H NMR (400 MHz,
CDCl3): δ = 7.60–7.59 (d, J = 7.6 Hz, 1 H), 7.31–7.29 (m, 4 H),
7.24–7.14 (m, 6 H), 6.96–6.92 (m, 1 H), 6.20–6.18 (d, J = 8.4 Hz,
1 H), 4.24–4.17 (m, 4 H), 3.70–3.55 (q, J = 16.4, 44.8 Hz, 2 H), 2.08
(s, 3 H), 1.27–1.22 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 170.3, 170.2, 141.9, 141.7, 141.4, 141.3, 136.4, 135.9, 135.5, 130.6,
129.9, 128.8, 128.3, 128.1, 127.7, 127.5, 126.8, 126.4, 124.3, 63.1,
61.8, 41.8, 19.5, 14.0 ppm. IR (KBr): ν = 3466, 2981, 1733, 1463,
˜
1258, 1050 cm–1. C29H28O4 (440.20): calcd. C 79.07, H 6.41; found
C 79.14, H 6.29.
IR (KBr): ν = 3467, 3348, 2982, 1732, 1683, 1600, 1465, 1362, 1264,
˜
1050 cm–1. C30H28O5 (468.19): calcd. C 76.90, H 6.02; found C
76.83, H 6.11.
Diethyl (Z)-3-[Phenyl(m-tolyl)methylene]-2,3-dihydroindene-1,1-di-
carboxylate (3g): The reaction mixture was purified by chromatog-
raphy with 20:1 hexanes/EtOAc to afford 76.6 mg (87%) of the title
compound as a solid; m.p. 84–86 °C. 1H NMR (400 MHz, CDCl3):
δ = 7.60–7.58 (m, 1 H), 7.34–7.27 (m, 4 H), 7.24–7.11 (m, 4 H),
7.05–6.94 (m, 3 H), 6.48–6.46 (d, J = 8.0 Hz, 1 H), 4.24–4.18 (m,
4 H), 3.51 (s, 2 H), 2.30 (s, 3 H), 1.27–1.23 (m, 6 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.2, 143.0, 141.9, 141.1, 138.3,
136.8, 135.4, 130.0, 128.9, 128.6, 128.1, 128.0, 127.6, 126.8, 126.6,
Compound 3m: The reaction mixture was purified by chromatog-
raphy with 20:1 hexanes/EtOAc to afford 97.5 mg (63%) of the title
1
compound as an oil. H NMR (400 MHz, CDCl3): δ = 7.61–7.59
(d, J = 8.0 Hz, 2 H), 7.46–7.43 (m, 4 H), 7.35–7.32 (m, 4 H), 7.22–
7.13 (m, 8 H), 6.98–6.94 (m, 2 H), 6.45–6.43 (d, J = 8.0 Hz, 2 H),
4.25–4.19 (m, 8 H), 3.48 (s, 4 H), 1.28–1.23 (m, 12 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.1, 142.1, 141.8, 141.5, 140.9,
136.3, 135.5, 131.3, 130.8, 129.7, 128.9, 128.0, 127.6, 126.6, 125.0,
126.4, 124.9, 63.0, 61.7, 42.1, 21.3, 14.0 ppm. IR (KBr): ν = 3467,
˜
2982, 1733, 1464, 1259, 1050 cm–1. C29H28O4 (440.20): calcd. C
79.07, H 6.41; found C 79.01, H 6.37.
120.9, 63.1, 61.9, 42.3, 14.0 ppm. IR (neat): ν = 3465, 2982, 1733,
˜
1485, 1391, 1259, 1240, 1070, 1011 cm–1. C50H46O8 (774.32): calcd.
C 77.50, H 5.98; found C 77.34, H 6.13.
Diethyl (Z)-3-[(3-Nitrophenyl)(phenyl)methylene]-2,3-dihydroindene-
1,1-dicarboxylate (3h): The reaction mixture was purified by
chromatography with 20:1 hexanes/EtOAc to afford 90.1 mg (96%)
of the title compound as a solid; m.p. 112–114 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.20–8.10 (m, 2 H), 7.66–7.61 (m, 2 H),
7.53–7.49 (m, 1 H), 7.38–7.20 (m, 6 H), 7.00–6.96 (m, 1 H), 6.43–
6.41 (d, J = 8.0 Hz, 1 H), 4.26–4.20 (m, 4 H), 3.53 (s, 2 H), 1.28–
1.24 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.9, 148.7,
143.7, 142.5, 141.7, 140.1, 137.8, 136.3, 133.8, 129.7, 129.0, 128.5,
128.1, 127.5, 126.9, 124.7, 124.4, 122.3, 63.0, 61.9, 42.5, 13.9 ppm.
Diethyl 4-(Diphenylmethylene)-1,2,3,4-tetrahydronaphthalene-2,2-
dicarboxylate (5a): The reaction mixture was purified by
chromatography with 20:1 hexanes/EtOAc to afford 81.8 mg (93%)
of the title compound as a solid; m.p. 98–100 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.33–7.23 (m, 3 H), 7.16–7.10 (m, 6 H),
7.04–6.97 (m, 3 H), 6.79–6.69 (m, 2 H), 4.18–4.11 (m, 2 H), 4.04–
3.98 (m, 2 H), 3.34 (s, 2 H), 3.13 (s, 2 H), 1.13–1.09 (m, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 171.0, 143.6, 143.1, 141.2, 135.9,
135.1, 131.0, 130.6, 130.4, 128.2, 128.0, 127.0, 126.7, 124.8, 61.4,
IR (KBr): ν = 3466, 2926, 1733, 1530, 1465, 1347, 1260, 1051 cm–1.
˜
55.0, 35.2, 34.9, 13.8 ppm. IR (KBr): ν = 3463, 2958, 1733, 1445,
˜
1367, 1255, 1184, 1053 cm–1. C29H28O4 (440.20): calcd. C 79.07, H
6.41; found C 79.01, H 6.43.
C28H25NO6 (471.17): calcd. C 71.33, H 5.34, N 2.97; found C
71.23, H 5.41, N 2.87.
Diethyl (Z)-3-[(2,6-Dimethoxyphenyl)(phenyl)methylene]-2,3-dihy-
droindene-1,1-dicarboxylate (3i): The reaction mixture was purified
by chromatography with 20:1 hexanes/EtOAc to afford 54.4 mg
(56%) of the title compound as a solid; m.p. 117–119 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.57–7.50 (dd, J = 0.8, 8.0 Hz, 1 H), 7.42–
7.39 (m, 2 H), 7.31–7.24 (m, 3 H), 7.21–7.14 (m, 2 H), 7.00–6.96
Diethyl (Z)-4-[Phenyl(p-tolyl)methylene]-1,2,3,4-tetrahydronaphtha-
lene-2,2-dicarboxylate (5c): The reaction mixture was purified by
chromatography with 20:1 hexanes/EtOAc to afford 83.5 mg (92%)
of the title compound as a solid; m.p. 87–89 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.32–7.23 (m, 3 H), 7.15–7.10 (m, 4 H),
7.04–6.81 (m, 5 H), 6.75–6.71 (m, 1 H), 4.17–4.11 (m, 2 H), 4.04–
(m, 1 H), 6.60–6.58 (d, J = 8.8 Hz, 2 H), 6.45–6.43 (d, J = 8.0 Hz, 3.98 (m, 2 H), 3.33 (s, 2 H), 3.11 (s, 2 H), 2.27 (s, 3 H), 1.14–1.09
1 H), 4.23–4.16 (m, 4 H), 3.58 (s, 6 H), 3.54 (s, 2 H), 1.25–1.22 (t,
J = 7.2 Hz, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.3,
157.8, 143.0, 141.9, 141.6, 136.7, 128.9, 128.5, 128.3, 127.8, 127.4,
126.4, 123.3, 119.8, 104.8, 63.1, 61.6, 55.9, 40.9, 13.9 ppm. IR
(m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.0, 143.3,
141.1, 140.6, 136.4, 136.2, 135.0, 131.0, 130.9, 130.4, 130.1, 128.7,
128.2, 127.9, 126.9, 126.7, 124.8, 61.4, 55.1, 35.3, 35.0, 21.2,
13.8 ppm. IR (KBr): ν = 3464, 2982, 1732, 1446, 1367, 1255, 1184,
˜
(KBr): ν = 3423, 2981, 1733, 1588, 1468, 1249, 1110, 1049 cm–1.
1053 cm–1. C30H30O4 (454.21): calcd. C 79.27, H 6.65; found C
79.34, H 6.53.
˜
C30H30O6 (486.20): calcd. C 74.06, H 6.21; found C 73.94, H 6.19.
1422
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1418–1425

Synthesis of Indene and Naphthalene Derivatives
Diethyl (Z)-4-[(4-Acetylphenyl)(phenyl)methylene]-1,2,3,4-tetra-
purified by chromatography with 20:1 hexanes/EtOAc to afford
85.5 mg (89%) of the title compound as an oil. 1H NMR
(300 MHz, CDCl3): δ = 8.68–8.65 (d, J = 7.5 Hz, 1 H), 7.70–7.67
(d, J = 8.1 Hz, 1 H), 7.59–7.56 (m, 2 H), 7.46–7.32 (m, 7 H), 6.89–
6.86 (d, J = 8.7 Hz, 2 H), 4.23–4.15 (m, 4 H), 3.80 (s, 3 H), 3.55
(s, 2 H), 1.26–1.21 (t, J = 7.2 Hz, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 169.9, 159.5, 143.5, 142.2, 140.7, 140.0, 132.8, 129.0,
hydronaphthalene-2,2-dicarboxylate (5d): The reaction mixture was
purified by chromatography with 20:1 hexanes/EtOAc to afford
81.9 mg (85%) of the title compound as an oil. 1H NMR
(400 MHz, CDCl3): δ = 7.75–7.72 (dd, J = 0.8, 8.8 Hz, 2 H), 7.35–
7.26 (m, 3 H), 7.15–7.06 (m, 6 H), 6.74–6.72 (m, 2 H), 4.18–4.14
(m, 2 H), 4.03–3.98 (m, 2 H), 3.35 (s, 2 H), 3.14 (s, 2 H), 2.53 (s, 3
H), 1.14–1.10 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 128.8, 128.5, 128.3, 127.4, 126.8, 124.5, 116.2, 115.6, 114.0, 95.3,
197.7, 170.9, 148.8, 142.3, 139.9, 135.5, 135.3, 132.6, 131.2, 130.5,
130.4, 128.3, 128.1, 127.5, 127.3, 125.0, 61.4, 55.0, 35.3, 34.8, 26.5,
89.1, 62.7, 61.9, 55.2, 41.0, 13.9 ppm. IR (neat): ν = 3459, 2981,
˜
1733, 1605, 1509, 1463, 1367, 1249, 1027 cm–1. C31H28O5 (480.19):
calcd. C 77.48, H 5.87; found C 77.69, H 5.77.
13.8 ppm. IR (neat): ν = 3462, 3346, 2983, 1731, 1682, 1600, 1445,
˜
1362, 1260, 1184, 1053 cm–1. C31H30O5 (482.21): calcd. C 77.16, H
6.27; found C 77.01, H 6.34.
(3Z)-Diethyl 3-(3-Cyclohexenyl-1-phenylprop-2-ynylidene)-2,3-dihy-
droindene-1,1-dicarboxylate (7c): The reaction mixture was purified
by chromatography with 20:1 hexanes/EtOAc to afford 78.6 mg
(87%) of the title compound as an oil. 1H NMR (300 MHz,
CDCl3): δ = 8.61–8.58 (d, J = 7.5 Hz, 1 H), 7.67–7.65 (d, J =
6.9 Hz, 1 H), 7.52–7.50 (d, J = 7.8 Hz, 2 H), 7.45–7.25 (m, 5 H),
6.18–6.17 (d, J = 4.2 Hz, 1 H), 4.24–4.13 (m, 4 H), 3.50 (s, 2 H),
2.25–2.14 (m, 4 H), 1.72–1.59 (m, 4 H), 1.25–1.20 (t, J = 7.2 Hz, 6
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.9, 142.9, 142.0,
140.7, 140.2, 135.2, 128.8, 128.6, 128.5, 128.2, 127.2, 126.7, 124.5,
121.0, 116.3, 97.4, 87.9, 62.7, 61.9, 40.9, 28.9, 25.7, 22.2, 21.4,
Diethyl (Z)-4-[Phenyl(o-tolyl)methylene]-1,2,3,4-tetrahydronaphtha-
lene-2,2-dicarboxylate (5f): The reaction mixture was purified by
chromatography with 20:1 hexanes/EtOAc to afford 81.1 mg (89%)
of the title compound as a solid; m.p. 110–112 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.30–7.26 (m, 2 H), 7.22–7.15 (m, 3 H),
7.09–6.91 (m, 6 H), 6.72–6.65 (m, 2 H), 4.19–4.09 (m, 3 H), 3.89–
3.84 (m, 1 H), 3.51–3.45 (m, 2 H), 3.16–3.02 (m, 2 H), 1.94 (s, 3 H),
1.18–1.14 (m, 3 H), 1.04–1.01 (m, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 171.2, 170.8, 143.0, 142.0, 140.6, 136.7, 136.1, 134.8,
131.2, 130.9, 130.2, 130.0, 129.2, 128.1, 127.9, 127.0, 126.7, 125.8,
13.9 ppm. IR (neat): ν = 3466, 2934, 1734, 1598, 1463, 1444, 1366,
˜
1257, 1240, 1050 cm–1. C30H30O4 (454.21): calcd. C 79.27, H 6.65;
found C 79.19, H 6.77.
125.0, 61.3, 54.9, 34.9, 34.5, 20.2, 13.9, 13.7 ppm. IR (KBr): ν =
˜
3464, 2982, 1732, 1446, 1367, 1256, 1185, 1117, 1053 cm–1.
C30H30O4 (454.21): calcd. C 79.27, H 6.65; found C 79.01, H 6.55.
Diethyl (Z)-3-[1-phenyl-3-(trimethylsilyl)prop-2-ynylidene]-2,3-dihy-
droindene-1,1-dicarboxylate (7d): The reaction mixture was purified
by chromatography with 20:1 hexanes/EtOAc to afford 81.2 mg
(91%) of the title compound as an oil. 1H NMR (300 MHz,
CDCl3): δ = 8.77–8.75 (d, J = 7.2 Hz, 1 H), 7.76–7.73 (dd, J = 1.5,
7.8 Hz, 1 H), 7.59–7.56 (d, J = 8.1 Hz, 2 H), 7.50–7.38 (m, 5 H),
4.29–4.22 (q, J = 7.2 Hz, 4 H), 3.57 (s, 2 H), 1.33–1.28 (t, J =
7.2 Hz, 6 H), 0.34 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
169.8, 145.4, 142.3, 140.3, 139.6, 129.2, 128.8, 128.5, 128.3, 127.4,
126.8, 124.9, 115.9, 105.5, 101.0, 62.6, 61.9, 41.0, 13.9, –0.2 ppm.
Diethyl
(Z)-4-[Phenyl(m-tolyl)methylene]-1,2,3,4-tetrahydronaph-
thalene-2,2-dicarboxylate (5g): The reaction mixture was purified
by chromatography with 20:1 hexanes/EtOAc to afford 83.5 mg
(92%) of the title compound as an oil. 1H NMR (400 MHz,
CDCl3): δ = 7.33–7.23 (m, 3 H), 7.16–7.09 (m, 3 H), 7.03–6.94 (m,
3 H), 6.80–6.72 (m, 4 H), 4.17–4.11 (m, 2 H), 4.04–3.98 (m, 2 H),
3.33 (s, 2 H), 3.11 (s, 2 H), 2.17 (s, 3 H), 1.13–1.09 (m, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 171.0, 143.5, 143.2, 141.3, 137.5,
136.1, 135.0, 131.4, 131.0, 130.4, 128.1, 127.9, 127.8, 127.6, 126.9,
IR (neat): ν = 3470, 2960, 2126, 1735, 1464, 1367, 1250, 1049 cm–1.
124.8, 61.4, 55.1, 35.3, 35.0, 21.3, 13.8 ppm. IR (neat): ν = 3464,
˜
˜
2982, 1732, 1600, 1446, 1367, 1255, 1185, 1053 cm–1. C30H30O4
(454.21): calcd. C 79.27, H 6.65; found C 79.09, H 6.47.
C27H30O4Si (446.19): calcd. C 72.61, H 6.77; found C 72.49, H
6.57.
General Procedure for the Preparation of 7 and 8: Pd(PPh3)2Cl2
(7 mg, 5 mol-%) and CuI (3.8 mg, 10 mol-%) were added to a solu-
tion of diethyl (2-iodophenyl)-2-(3-arylprop-2-ynyl)malonate or di-
ethyl (2-iodobenzyl)-2-(3-phenylprop-2-ynyl)malonate (1 or 4;
0.20 mmol), alkyne (0.30 mmol) and Et3N (40.4 mg, 0.40 mmol) in
DMF (2.0 mL). The resulting mixture was then heated under argon
at 100 °C. The work-up procedure was the same as that described
for the Heck/Suzuki–Miyaura domino reaction. The residue was
purified by chromatography on silica gel to afford the correspond-
ing substituted indene (7) or naphthalene (8) derivatives.
Diethyl (Z)-3-(1-Phenyloct-2-ynylidene)-2,3-dihydroindene-1,1-di-
carboxylate (7e): The reaction was run at 60 °C. The reaction mix-
ture was purified by chromatography with 20:1 hexanes/EtOAc to
afford 37.3 mg (42%) of the title compound as an oil. 1H NMR
(300 MHz, CDCl3): δ = 8.62–8.60 (d, J = 7.8 Hz, 1 H), 7.67–7.64
(d, J = 7.5 Hz, 1 H), 7.51–7.48 (d, J = 7.5 Hz, 2 H), 7.41–7.25 (m,
5 H), 4.21–4.14 (q, J = 7.2 Hz, 4 H), 3.47 (s, 2 H), 2.51–2.46 (t, J
= 7.2 Hz, 2 H), 1.67–1.58 (m, 2 H), 1.48–1.27 (m, 4 H), 1.25–1.20
(t, J = 7.5 Hz, 6 H), 0.94–0.89 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.0, 142.5, 141.9, 140.8, 128.8, 128.5,
128.3, 127.2, 126.7, 124.3, 116.5, 97.2, 81.4, 62.7, 61.9, 40.8, 31.2,
Diethyl (Z)-3-(1,3-Diphenylprop-2-ynylidene)-2,3-dihydroindene-1,1-
dicarboxylate (7a): The reaction mixture was purified by
chromatography with 20:1 hexanes/EtOAc to afford 76.5 mg (85%)
28.3, 22.2, 19.9, 14.0 ppm. IR (neat): ν = 3470, 2960, 2932, 1735,
˜
1463, 1367, 1261, 1239, 1049 cm–1. C29H32O4 (444.23): calcd. C
78.35, H 7.26; found C 78.29, H 7.17.
1
of the title compound as an oil. H NMR (300 MHz, CDCl3): δ =
8.68–8.65 (d, J = 7.5 Hz, 1 H), 7.70–7.68 (d, J = 7.8 Hz, 1 H),
7.59–7.30 (m, 12 H), 4.26–4.16 (m, 4 H), 3.55 (s, 2 H), 1.26–1.22
(t, J = 7.2 Hz, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.9,
144.4, 142.3, 140.6, 139.9, 131.4, 129.2, 128.8, 128.6, 128.4, 128.2,
127.5, 126.8, 124.7, 123.5, 115.9, 95.2, 90.4, 62.8, 62.0, 41.1,
Diethyl
(Z)-4-(1,3-Diphenylprop-2-ynylidene)-1,2,3,4-tetrahydro-
naphthalene-2,2-dicarboxylate (8a): The reaction mixture was puri-
fied by chromatography with 20:1 hexanes/EtOAc to afford 76.1 mg
(82%) of the title compound as a solid; m.p. 116–118 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.56–8.53 (dd, J = 3.6, 5.4 Hz, 1 H), 7.48–
7.38 (m, 4 H), 7.34–7.17 (m, 9 H), 4.14–3.98 (m, 4 H), 3.29 (s, 2
H), 3.15 (s, 2 H), 1.12–1.07 (t, J = 7.2 Hz, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.6, 139.9, 138.9, 135.1, 134.9, 131.3,
129.2, 128.6, 128.5, 128.3, 128.2, 127.9, 127.4, 125.6, 123.7, 120.7,
14.0 ppm. IR (neat): ν = 3466, 2981, 1734, 1489, 1444, 1367, 1258,
˜
1241, 1195, 1050 cm–1. C30H26 O (450.18): calcd. C 79.98, H 5.82;
found C 79.79, H 5.87.
Diethyl (Z)-3-[3-(4-Methoxyphenyl)-1-phenylprop-2-ynylidene]-2,3-
dihydroindene-1,1-dicarboxylate (7b): The reaction mixture was
93.4, 92.0, 61.5, 54.7, 35.4, 35.1, 13.8 ppm. IR (KBr): ν = 3462,
˜
Eur. J. Org. Chem. 2008, 1418–1425
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1423

L.-N. Guo, X.-H. Duan, J. Hu, H.-P. Bi, X.-Y. Liu, Y.-M. Liang
FULL PAPER
2982, 1733, 1489, 1444, 1258, 1184, 1071, 1049 cm–1. C31H28O4
(464.20): calcd. C 80.15, H 6.08; found C 80.29, H 6.17.
96, 115–136; b) M. Malacria, Chem. Rev. 1996, 96, 289–306; c)
S.-i. Ikeda, Acc. Chem. Res. 2000, 33, 511–519, and references
cited therein; d) G. Battistuzzi, S. Cacchi, G. Fabrizi, Eur. J.
Org. Chem. 2002, 2671–2681; e) G. Balme, E. Bossharth, N.
Monteiro, Eur. J. Org. Chem. 2003, 4101–4111.
Diethyl
(Z)-4-[3-(4-Methoxyphenyl)-1-phenylprop-2-ynylidene]-
1,2,3,4-tetrahydronaphthalene-2,2-dicarboxylate (8b): The reaction
mixture was purified by chromatography with 20:1 hexanes/EtOAc
to afford 72.1 mg (73%) of the title compound as a solid; m.p. 134–
136 °C. 1H NMR (300 MHz, CDCl3): δ = 8.57–8.55 (m, 1 H), 7.47–
7.38 (m, 4 H), 7.34–7.18 (m, 6 H), 6.81–6.79 (dd, J = 1.2, 6.6 Hz,
2 H), 4.15–3.99 (m, 4 H), 3.77 (s, 3 H), 3.28 (s, 2 H), 3.14 (s, 2 H),
1.12–1.08 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.7,
159.5, 140.1, 137.9, 135.1, 132.8, 129.3, 128.6, 128.3, 127.4, 125.6,
120.9, 115.9, 113.9, 93.7, 90.9, 61.5, 55.2, 54.7, 35.5, 35.1,
[2]
For reviews covering Pd-catalyzed domino reactions, see: a) W.
Oppolzer, Comprehensive Organometallic Chemistry II (Eds.:
E. W. Abel, F. G. A. Stone, G. Wilkinson), Pergamon Press,
Oxford, 1995, vol. 12, p. 905; b) R. Grigg, V. Sridharan, Com-
prehensive Organometallic Chemistry II (Eds.: E. W. Abel,
F. G. A. Stone, G. Wilkinson), Pergamon Press, Oxford, 1995,
vol. 12, p. 299; c) E.-i. Negishi, C. Copéret, S. Ma, S.-Y. Liou,
F. Liu, Chem. Rev. 1996, 96, 365–394; d) I. Ojima, M. Tzamari-
oudaki, Z. Li, R. J. Donovan, Chem. Rev. 1996, 96, 635–662;
e) R. Grigg, V. Sridharan, Pure Appl. Chem. 1998, 70, 1047–
1057; f) R. Grigg, V. Sridharan, J. Organomet. Chem. 1999,
576, 65–87; g) R. Grigg, V. Sridharan, IUPAC Monograph
(Eds.: S. G. Davies, S.-I. Murahashi), Blackwell, New York,
1999; vol. 576, p. 87; h) A. de Meijere, S. Bräse, J. Organomet.
Chem. 1999, 576, 88–110; i) R. C. Larock, Pure Appl. Chem.
1999, 71, 1435–1442; j) G. Poli, G. Giambastiani, A. Heumann,
Tetrahedron 2000, 56, 5959–5989; k) G. Balme, D. Bouyssi, T.
Lomberget, N. Monteiro, Synthesis 2003, 2115–2134; l) A.
de Meijere, P. von Zezschwitz, S. Bräse, Acc. Chem. Res. 2005,
38, 413–422.
For some recent examples, see: a) R.-T. Wang, F.-L. Chou, F.-
T. Luo, J. Org. Chem. 1990, 55, 4846–4849; b) F.-T. Luo, R.-T.
Wang, Tetrahedron Lett. 1991, 32, 7703–7706; c) M. Lshikura,
J. Chem. Soc. Chem. Commun. 1995, 409–410; d) Y.-H. Ha, S.-
K. Kang, Org. Lett. 2002, 4, 1143–1146; e) C. H. Oh, Y. M.
Lim, Tetrahedron Lett. 2003, 44, 267–270; f) H. Ohno, K. Mi-
yamura, Y. Takeoka, T. Tanaka, Angew. Chem. Int. Ed. 2003,
42, 2647–2650; g) G. Zhu, Z. Zhang, Org. Lett. 2003, 5, 3645–
3648; h) F. F. Kneisel, M. Dochnahl, P. Knochel, Angew. Chem.
Int. Ed. 2004, 43, 1017–1021; i) C. J. Kressierer, T. J. J. Müller,
Angew. Chem. Int. Ed. 2004, 43, 5997–6000; j) G. Zhu, Z.
Zhang, Org. Lett. 2004, 6, 4041–4044; k) G. Zhu, X. Tong, J.
Cheng, Y. Sun, D. Li, Z. Zhang, J. Org. Chem. 2005, 70, 1712–
1717; l) A. Pinto, L. Neuville, P. Retailleau, J. Zhu, Org. Lett.
2006, 8, 4927–4930, and references cited therein; m) M. Ishi-
kura, N. Takahashi, K. Yamada, R. Yanada, Tetrahedron 2006,
62, 11580–11591.
13.8 ppm. IR (neat): ν = 2984, 2254, 1729, 1606, 1509, 1370, 1248,
˜
1030 cm–1. C32H30O5 (494.21): calcd. C 77.71, H 6.11; found C
77.58, H 6.13.
Diethyl (4Z)-4-(3-Cyclohexenyl-1-phenylprop-2-ynylidene)-1,2,3,4-
tetrahydronaphthalene-2,2-dicarboxylate (8c): The reaction mixture
was purified by chromatography with 20:1 hexanes/EtOAc to afford
56.2 mg (60%) of the title compound as an oil. 1H NMR
(300 MHz, CDCl3): δ = 8.51–8.49 (m, 1 H), 7.40–7.35 (m, 4 H),
7.30–7.14 (m, 4 H), 6.01–6.00 (t, J = 1.2 Hz, 1 H), 4.12–3.97 (m, 4
H), 3.25 (s, 2 H), 3.09 (s, 2 H), 2.10–2.06 (m, 4 H), 1.61–1.54 (m,
4 H), 1.11–1.07 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
170.7, 140.4, 137.3, 135.1, 134.8, 129.2, 128.5, 128.2, 127.2, 125.5,
121.2, 121.1, 95.8, 89.5, 61.4, 54.7, 35.5, 35.1, 28.6, 25.7, 22.2, 21.5,
[3]
13.8 ppm. IR (neat): ν = 2933, 2254, 1730, 1443, 1393, 1368, 1260,
˜
1050 cm–1. C31H32O4 (468.23): calcd. C 79.46, H 6.88; found C
79.58, H 6.75.
General Procedure for the Preparation of 9: A mixture of diethyl 2-
(2-iodophenyl)-2-(3-phenylprop-2-ynyl)malonate (1a; 0.20 mmol),
methyl acrylate (0.24 mmol), Et3N (40.4 mg, 0.40 mmol), Pd-
(PPh3)4 (11.5 mg, 5 mol-%) and DMF (2.0 mL) was placed in a
25 mL flask under argon. The resulting mixture was then heated
under argon at 100 °C. The work-up procedure was the same as
that described for Heck/Suzuki–Miyaura domino reaction. The res-
idue was purified by chromatography on silica gel to afford the
corresponding substituted indene derivatives 9.
[4]
For Pd-catalyzed Heck cyclization/Suzuki–Miyaura coupling
reactions, see: a) S. Couty, B. Liégault, C. Meyer, J. Cossy, Org.
Lett. 2004, 6, 2511–2514; b) W. S. Cheung, R. J. Patch, M. R.
Player, J. Org. Chem. 2005, 70, 3741–3744; c) R. Yanada, S.
Obika, T. Inokuma, K. Yanada, M. Yamashita, S. Ohta, Y.
Takemoto, J. Org. Chem. 2005, 70, 6972–6975; d) H. Yu, R. N.
Richey, M. W. Carson, M. J. Coghlan, Org. Lett. 2006, 8, 1685–
1688, and references cited therein.
Diethyl 3-[(E,E)-3-(Methoxycarbonyl)-1-phenylallylidene]-2,3-dihy-
droindene-1,1-dicarboxylate [(E,E)-9]: The reaction mixture was
purified by chromatography with 20:1 hexanes/EtOAc to afford
69.4 mg (80%) of the title compound as a solid; m.p. 114–116 °C.
1H NMR (400 MHz, CDCl3): δ = 8.44–8.40 (d, J = 15.6 Hz, 1 H),
7.84–7.83 (d, J = 7.6 Hz, 1 H), 7.71–7.69 (d, J = 7.2 Hz, 1 H),
7.49–7.36 (m, 5 H), 7.23–7.21 (m, 2 H), 5.56–5.52 (d, J = 15.6 Hz,
1 H), 4.20–4.13 (m, 4 H), 3.75 (s, 3 H), 3.20 (s, 2 H), 1.26–1.21 (m,
6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.6, 167.9, 145.1,
143.5, 143.1, 139.7, 139.4, 133.3, 129.3, 129.2, 128.8, 127.6, 127.3,
[5]
[6]
For Pd-catalyzed Heck cyclization/Sonogashira coupling reac-
tions, see: a) F. Teplý, I. G. Stará, I. Starý, A. Kollárovicˇ, D.
ˇ
Saman, P. Fiedler, Tetrahedron 2002, 58, 9007–9018; b) D. M.
D’Souza, F. Rominger, T. J. J. Müller, Angew. Chem. Int. Ed.
2005, 44, 153–158.
126.0, 121.5, 62.9, 61.9, 51.5, 43.0, 13.9 ppm. IR (KBr): ν = 3407,
˜
2925, 1731, 1612, 1461, 1368, 1260, 1170, 1092, 1048, 1028 cm–1.
C26H26O6 (434.17): calcd. C 71.87, H 6.03; found C 71.69, H 6.15.
For reviews, see: a) R. C. Larock, J. Organomet. Chem. 1999,
576, 111–124; b) S. Cacchi, J. Organomet. Chem. 1999, 576,
42–64; c) I. Nakamura, Y. Yamamoto, Chem. Rev. 2004, 104,
2127–2198; d) G. Zeni, R. C. Larock, Chem. Rev. 2004, 104,
2285–2310; e) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev.
2004, 104, 3079–3160; f) S. Cacchi, G. Fabrizi, Chem. Rev.
2005, 105, 2873–2920; g) G. Zeni, R. C. Larock, Chem. Rev.
2006, 106, 4644–4680, and references cited therein.
Supporting Information (see also the footnote on the first page of
this article): Typical experimental characterization for all products.
Acknowledgments
[7]
[8]
a) L.-N. Guo, X.-H. Duan, H.-P. Bi, X.-Y. Liu, Y.-M. Liang,
J. Org. Chem. 2006, 71, 3325–3327; b) X.-H. Duan, L.-N. Guo,
H.-P. Bi, X.-Y. Liu, Y.-M. Liang, Org. Lett. 2006, 8, 3053–3056.
Crystal data for (Z)-3d: C30H28O5, Mw = 468.52, T = 294(2) K,
λ = 0.71073 Å, monoclinic space group P1, a = 8.5245(5), b =
36.609(2), c = 16.3840(9) Å, α = 90.00, β = 91.0620(10), γ =
90.00°, V = 5112.2(5) Å3, Z = 4, Dc = 1.217 mgm–3, µ =
We thank the Chinese National Science Foundation (NSF) (NSF-
20621091, NSF-20672049) and the “Hundred Scientist Program”
of the Chinese Academy of Sciences for financial support.
[1] For reviews of domino (cascade) reactions catalyzed by transi-
tion metals, see, for example: a) L. F. Tietze, Chem. Rev. 1996,
1424
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1418–1425

Synthesis of Indene and Naphthalene Derivatives
0.082 mm–1, F(000) = 1984, crystal size 0.28ϫ0.24ϫ0.20 mm,
independent reflections 9510 [R(int) = 0.0433], 26615 reflec-
tions collected, refinement method, full-matrix least-squares on
F2, goodness-of-fit on F2 1.054, final R indices [IϾ2σ(I)] R1 =
0.1176, wR2 = 0.1607, R indices (all date) R1 = 0.0554, wR2 =
0.1295, extinction coefficient 0.0017(6), largest diff. peak and
hole 0.275 and –0.204 eÅ–3. CCDC-650940 contains the sup-
plementary crystallographic data for (Z)-3d. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[9] The stereoselectivity of compounds 7 and 8 was unambigu-
ously confirmed by the NOESY spectroscopy.
[10] Similar results were observed in a Pd-catalyzed domino reac-
tion, see: Y. Zhang, E-i. Negishi, J. Am. Chem. Soc. 1989, 111,
1
3454–3957. The ratio was determined by H NMR analysis of
the product.
[11] C. Amatore, S. Bensalem, S. Ghalem, A. Jutand, J. Organomet.
Chem. 2004, 689, 4642–4646.
Received: November 5, 2007
Published Online: January 15, 2008
Eur. J. Org. Chem. 2008, 1418–1425
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1425